Evaluation of Brain Lesions in HIV-infected Patients for Diagnosis of Primary Central Nervous System Lymphoma

This study has been completed.

Sponsor:

National Institutes of Health Clinical Center (CC)

ClinicalTrials.gov Identifier:

NCT00226304

First Posted: September 26, 2005

Last Update Posted: July 2, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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Evaluation of Brain Lesions in HIV-infected Patients for Diagnosis of Primary Central Nervous System Lymphoma

Official Title

The Evaluation of Focal Contrast-Enhancing Brain Lesions in HIV-Infected Patients

Brief Summary

This study will evaluate the usefulness of two tests in quickly distinguishing whether a patient with HIV infection and focal brain lesions (an injury in a specific area of the brain) has a rare type of cancer called primary central nervous system lymphoma (PCNSL), or a parasitic infection called toxoplasmic encephalitis.

Toxoplasmic encephalitis is caused by a parasite and can be treated with antibiotics. PCNSL (lymphoma of the brain or spinal cord) must be definitively diagnosed with a brain biopsy (removal of a small piece of brain tissue), and the treatment is radiation therapy and chemotherapy.

The tests under study for diagnosing PCNSL or toxoplasmic encephalitis are measurement of Epstein Barr virus (EBV) DNA in cerebrospinal fluid (CSF) and FDG-PET scan of the brain. EBV is often found in the CSF of people with PCNSL. The study also will compare the accuracy of two imaging techniques-TI-SPECT and FDG-PET-in distinguishing between toxoplasmosis and PCNSL.

Patients 18 years of age and older who have HIV infection and at least one focal brain lesion without a prior history of PCNSL or toxoplasmic encephalitis may be eligible for this study. Each candidate is screened with a medical history, physical examination, blood and urine tests and MRI scans of the brain.

Upon entering the study, all participants take medication to treat toxoplasmic encephalitis. They undergo lumbar puncture (spinal tap) to obtain CSF for analysis, an FDG-PET scan, and a 201TI-SPECT scan. For the PET scan, a radioactive substance is injected into an arm, followed by scanning in a doughnut-shaped machine similar to a CT scanner. SPECT is similar to PET but uses a different radioactive tracer, and the patient lies on a table while the SPECT camera rotates around the patient's head. Patients whose test results indicate a low risk for lymphoma continue antibiotic therapy for toxoplasmosis. They have repeat MRI scans around 4, 7, and 14 days after starting the drug to monitor the response to therapy. Antiretroviral therapy is initiated in patients who are not already on such a regimen.

Patients whose test results indicate a high risk for PCNSL have a CT scan to look for evidence of lymphoma elsewhere in the body and are referred for consultation with a neurosurgeon to discuss undergoing a brain biopsy. The brain biopsy is done in the operating room under general anesthesia. A small cut is made in the scalp and a small opening is made in the skull over the area of the brain to be biopsied. A needle is placed in the opening in the skull and, guided by CT or MRI, moved to the abnormal area of the brain, where a small piece of tissue is removed for study under a microscope.

Patients found to have toxoplasmosis are discharged from the hospital to the care of their primary care physician after they are getting better and are tolerating all their medications. They return to NIH for follow-up visits about 4 weeks, and 6 months after discharge.

Patients found to have lymphoma are referred to the National Cancer Institute for screening for enrollment in a treatment protocol. Patients who are not eligible for a treatment protocol are referred back to their primary care physician or for another NIH treatment protocol, if one is available. Patients with lymphoma are seen at the NIAID outpatient clinic for follow-up visits and laboratory examinations every 3 months for 2 years.

Detailed Description

Epstein Barr Virus (EBV)-associated primary central nervous system lymphoma (PCNSL) remains a major problem among AIDS patients. The clinical presentation is often clinically indistinguishable from toxoplasmic encephalitis. The method of choice for establishing the definitive diagnosis is brain biopsy. This procedure can be associated with a significant morbidity and mortality, and therefore less invasive means of diagnosing cerebral mass lesions have been studied.

Currently, an accepted standard of care for HIV-infected patients that present with signs and symptoms of focal brain lesions is to empirically treat for toxoplasmic encephalitis. Brain biopsy is often deferred until there is demonstration of lack of clinical response or progression on empiric therapy. As a result, treatment initiation is frequently delayed. During this time it is not unusual for further clinical deterioration to occur before appropriate therapies can be initiated. Frequently, the alternative approaches then become a question of appropriate palliation rather than curative intent therapy.

Less invasive diagnostic tests to assist in the diagnosis have been investigated. Based on the finding that essentially 100% of HIV-related PCNSL are EBV-associated, the detection of EBV DNA by PCR amplification in the cerebrospinal fluid (CSF) has demonstrated clinical usefulness in the diagnosis, as has the use of neuroradiologic imaging to detect the malignancy. Prior studies have demonstrated that the use of a combination of neuroradiologic, immunologic, and clinical variables in the workup of focal brain lesions in HIV-infected patients to be quite accurate in identifying patients in need of brain biopsy, but a diagnostic algorithm that incorporates the combination of the most sensitive and specific tests in a timely manner has not yet been explored.

This study seeks to evaluate an algorithm for the workup of HIV infected patients with focal brain lesions so as to expedite the diagnosis and subsequent treatment of PCNSL. The goals of the study are to 1) determine the specificity, sensitivity, and positive predictive value of a diagnostic algorithm that entails the use of the combination of EBV detection in the CSF and FDG-PET scanning to diagnose PCNSL; 2) evaluate the time to response to anti-toxoplasmic encephalitis therapy, and 3) evaluate the sensitivities and specificities of FDG-PET and (201)Tl-SPECT scanning in identifying PCNSL. Up to one hundred HIV-infected patients with history of at least one focal brain lesion will be screened for enrollment. All patients will be treated empirically for toxoplasmic encephalitis until an alternative diagnosis is confirmed. All enrolled patients will be treated concurrently with antiretroviral therapy. Patients identified to have PCNSL will be referred to the NCI Treatment of PCNSL Protocol for further treatment if the study is open for enrollment.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status

Completed

Enrollment

120

Estimated Completion Date

April 15, 2009

Primary Completion Date

Not Provided

Eligibility Criteria

INCLUSION CRITERIA:

Adult (18 years old or older) HIV-infected patient

HIV infected by OraQuick rapid test using saliva, venipuncture whole blood, or fingerstick whole blood; or by reactive ELISA and Western Blot as determined by an outside CLIA-approved laboratory facility or by NIH Clinical Pathology Laboratory or SAIC-Frederick Inc Monitoring Laboratory. HIV infection as determined by an outside CLIA-approved laboratory facility will be verified by a standard HIV-1 ELISA with Western Blot confirmation prior to brain biopsy.

Evidence of contrast-enhancing focal brain lesion(s) as seen on MRI or CT

Willingness to give informed consent and provided by Durable Power of Attorney. In the event that no Durable Power of Attorney has been designated and the patient is unable to do so, the NIH Ethics Committee will be consulted. All patients must designate a Durable Power of Attorney in order to participate in the study.